The project which is covered in this report is a study of 1) the biosynthesis and metabolism of Gamma-hydroxybutyrate (GHB), a naturally occurring, neuroactive compound and 2) the role which this compound plays in the central nervous system. Several pathways of biosynthesis are currently being investigated. Studies of the enzyme which plays a major role in the degradation of GHB are continuing. A new emphasis will be placed on studies of the role of GHB in the central nervous system, on the relationship of GHB to the opiates and on the mechanisms by which GHB exerts its profound physiological effects. A screening project to detect patients with defects in GHB metabolism has been started.